Rising prostate-specific antigen (PSA) levels after radical therapy are indicative
of recurrent or residual prostate cancer (PCa). This biochemical recurrence typically
predates clinically detectable metastatic disease by several years. Management of
patients with biochemical recurrence is controversial.
To assess the effect of dutasteride on progression of PCa in patients with biochemical
failure after radical therapy.
Design, setting, and participants
Randomised, double-blind, placebo-controlled trial in 294 men from 64 centres across
9 European countries.
The 5α-reductase inhibitor, dutasteride.
Outcome measurements and statistical analysis
The primary end point was time to PSA doubling from start of randomised treatment,
analysed by log-rank test stratified by previous therapy and investigative-site cluster.
Secondary end points included time to disease progression and the proportion of subjects
with disease progression.
Results and limitations
Of the 294 subjects randomised (147 in each treatment group), 187 (64%) completed
24 mo of treatment and 107 discontinued treatment prematurely (71 [48%] of the placebo
group, 36 [24%] of the dutasteride group). Dutasteride significantly delayed the time
to PSA doubling compared with placebo after 24 mo of treatment (p < 0.001); the relative risk (RR) reduction was 66.1% (95% confidence interval [CI],
50.35–76.90) for the overall study period. Dutasteride also significantly delayed
disease progression (which included PSA- and non-PSA-related outcomes) compared with
placebo (p < 0.001); the overall RR reduction in favour of dutasteride was 59% (95% CI, 32.53–75.09).
The incidence of adverse events (AEs), serious AEs, and AEs leading to study withdrawal
were similar between the treatment groups. A limitation was that investigators were
not blinded to PSA levels during the study.
Dutasteride delayed the biochemical progression of PCa in patients with biochemical
failure after radical therapy for clinically localised disease. The safety and tolerability
of dutasteride were generally consistent with previous experience.
Clinical trial registry